Influence of treatment with neutralizing monoclonal antibodies on the SARS-CoV-2 nasopharyngeal load and quasispecies

Camille Vellas (1, 2) , Arnaud del Bello (2, 3) , Alexa Debard (4) , Zara Steinmeyer (5) , Laure Tribaudeau (6, 5) , Noémie Ranger (1) , Nicolas Jeanne (1) , Guillaume Martin-Blondel (4, 2) , Pierre Delobel (2, 4) , Nassim Kamar (3, 2) , Jacques Izopet (2, 1)

1 Laboratoire Virologie [CHU Toulouse]
2 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
3 Service de Néphrologie - Immunologie Clinique [Toulouse]
4 Service Maladies infectieuses et tropicales [CHU Toulouse]
5 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
6 UT3 - Université Toulouse III - Paul Sabatier

Objectives: To evaluate the impact of neutralizing monoclonal antibody (mAb) treatment and to determine whether the selective pressure of mAbs could facilitate the proliferation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with spike protein mutations that might attenuate mAb effectiveness.Patients and methods: We evaluated the impact of mAbs on the nasopharyngeal (NP) viral load and virus quasispecies of mAb-treated patients using single-molecule real-time sequencing. The mAbs used were: Bamlanivimab alone (four patients), Bamlanivimab/Etesevimab (23 patients) and Casirivimab/Imdevimab (five patients).Results: The NP SARS-CoV-2 viral load of mAb-treated patients decreased from 8.2 log10 copies/mL before administration to 4.3 log10 copies/mL 7 days after administration. Five immunocompromised patients given Bamlanivimab/Etesevimab were found to have mAb activity-reducing spike mutations. Two patients harboured SARS-CoV-2 variants with a Q493R spike mutation 7 days after administration, as did a third patient 14 days after administration. The fourth patient harboured a variant with a Q493K spike mutation 7 days post-treatment, and the fifth patient had a variant with a E484K spike mutation on day 21. The emergence of the spike mutation was accompanied by stabilization or rebound of the NP viral load in three of five patients.Conclusion: Two-mAb therapy can drive the selection of resistant SARS-CoV-2 variants in immunocompromised patients. Patients given mAbs should be closely monitored and measures to limit virus spread should be reinforced.

Mots clés: Coronavirus disease 2019; Mutations; Neutralizing monoclonal antibodies; Quasispecies; Receptor-binding domain; Severe acute respiratory syndrome coronavirus 2; Single-molecular real-time sequencing; Spike protein

Domaines: Sciences du Vivant [q-bio]; Immunologie; Santé publique et épidémiologie

Camille Vellas, Arnaud del Bello, Alexa Debard, Zara Steinmeyer, Laure Tribaudeau, et al.. Influence of treatment with neutralizing monoclonal antibodies on the SARS-CoV-2 nasopharyngeal load and quasispecies. Clinical Microbiology and Infection, 2022, 28 (1), pp.139.e5-139.e8. ⟨10.1016/j.cmi.2021.09.008⟩. ⟨hal-03690064⟩